tbuckley/cabot-search huggingface dataset:
Impaired IL-23–dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency
Authors: Masato Ogishi, Andrés Augusto Arias, Rui Yang, Ji Eun Han, Peng Zhang, Darawan Rinchai, Joshua Halpern, Jeanette Mulwa, Narelle Keating, Maya Chrabieh, Candice Lainé, Yoann Seeleuthner, Noé Ramírez-Alejo, Nioosha Nekooie-Marnany, Andrea Guennoun, Ingrid Muller-Fleckenstein, Bernhard Fleckenstein, Sara S. Kilic, Yoshiyuki Minegishi, Stephan Ehl, Petra Kaiser-Labusch, Yasemin Kendir-Demirkol, Flore Rozenberg, Abderrahmane Errami, Shen-Ying Zhang, Qian Zhang, Jonathan Bohlen, Quentin Philippot, Anne Puel, Emmanuelle Jouanguy, Zahra Pourmoghaddas, Shahrzad Bakhtiar, Andre M. Willasch, Gerd Horneff, Genevieve Llanora, Lynette P. Shek, Louis Y.A. Chai, Sen Hee Tay, Hamid H. Rahimi, Seyed Alireza Mahdaviani, Serdar Nepesov, Aziz A. Bousfiha, Emine Hafize Erdeniz, Adem Karbuz, Nico Marr, Carmen Navarrete, Mehdi Adeli, Lennart Hammarstrom, Hassan Abolhassani, Nima Parvaneh, Saleh Al Muhsen, Mohammed F. Alosaimi, Fahad Alsohime, Maryam Nourizadeh, Mostafa Moin, Rand Arnaout, Saad Alshareef, Jamila El-Baghdadi, Ferah Genel, Roya Sherkat, Ayça Kiykim, Esra Yücel, Sevgi Keles, Jacinta Bustamante, Laurent Abel, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis
Journal: The Journal of Experimental Medicine (2022)

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Tγδ LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137 patients
Authors: Gregorio Barilà, Angela Grassi, HeeJin Cheon, Antonella Teramo, Giulia Calabretto, Jasmanet Chahal, Cristina Vicenzetto, Julia Almeida, Bryna C. Shemo, Min Shi, Vanessa Rebecca Gasparini, Noemi Munoz-Garcia, Cédric Pastoret, Hideyuki Nakazawa, Kazuo Oshimi, Lubomir Sokol, Fumihiro Ishida, Thierry Lamy, Alberto Orfao, William G. Morice, Thomas P. Loughran, Gianpietro Semenzato, Renato Zambello
Journal: Blood (2022)

Tγδ large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent Tαβ LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by Tγδ LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in ∼20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of Tγδ cases were also compared with a recently published Tαβ cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, Tγδ cases more frequently presented with neutropenia (P = .0161), anemia (P < .0001), severe anemia (P = .0065), and thrombocytopenia (P = .0187). Moreover, Vδ2- cases displayed higher frequency of symptomatic disease. Overall, Tγδ cases displayed reduced survival with respect to Tαβ cases (P = .0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tγδ LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with Tαβ LGLL.
Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial
Authors: Fabio Conforti, Paolo Andrea Zucali, Laura Pala, Chiara Catania, Vincenzo Bagnardi, Isabella Sala, Paolo Della Vigna, Matteo Perrino, Paola Zagami, Chiara Corti, Sara Stucchi, Massimo Barberis, Elena Guerini-Rocco, Benedetta Di Venosa, Fabio De Vincenzo, Nadia Cordua, Armando Santoro, Giuseppe Giaccone, Tommaso Martino De Pas
Journal: The Lancet Oncology (2022)
Thresholds for Hypertension Definition, Treatment Initiation, and Treatment Targets: Recent Guidelines at a Glance
Authors: Emmanuelle Vidal-Petiot
Journal: Circulation (2022)

ome physicians may be nostalgic for the years 2011 to 2015, back when most hypertension guidelines agreed to use a threshold of 140/90 mm Hg to define hypertension, to initiate drug treatment, and as a treatment target in the majority of adult patients (except in elderly adults, for whom higher values were tolerated).Since then, one of the most-if not the most-important trial in the field of hypertension, SPRINT (Systolic Blood Pressure Intervention Trial), showed that targeting systolic blood pressure (SBP) <120 mm Hg in patients at high cardiovascular risk resulted in lower rates of cardiovascular events and mortality compared with standard treatment (<140 mm Hg), and led scientific societies to reconsider guidelines.
Simulation of Long-term Outcomes in Patients With Nonalcoholic Fatty Liver Disease
Authors: Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang
Journal: JAMA Network Open (2022)

Jagpreet Chhatwal, PhD; Ozden O. Dalgic, PhD; Wanyi Chen, PhD; Sumeyye Samur, PhD; Emily D. Bethea, MD; Jade Xiao, BE; Chin Hur, MD, MPH; Kathleen E. Corey, MD, MPH, MMSc; Rohit Loomba, MD, MHSc
This Month's Highlights
Journal: Journal of the American Society of Nephrology (2022)

Corresponding Article Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy Reinhard, Linda; Machalitza, Maya; Wiech, Thorsten; Gröne, Hermann-Josef; Lassé, Moritz; Rinschen, Markus M.; Ferru, Nicoletta; Bräsen, Jan Hinrich; Drömann, Friederike; Rob, Peter Maria; Sethi, Sanjeev; Hoxha, Elion; Stahl, Rolf A.K. Journal of the American Society of Nephrology. 33(10):1823-1831, October 2022. Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study Swartling, Oskar; Yang, Yuanhang; Clase, Catherine M.; Fu, Edouard L.; Hecking, Manfred; Hödlmoser, Sebastian; Trolle-Lagerros, Ylva; Evans, Marie; Carrero, Juan J. Journal of the American Society of Nephrology. 33(10):1903-1914, October 2022. Sex Disparities in the Quality of Care for CKD Reaves, Allison C.; Levey, Andrew S. Journal of the American Society of Nephrology. 33(10):1804-1806, October 2022. Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies Denic, Aleksandar; Bogojevic, Marija; Mullan, Aidan F.; Sabov, Moldovan; Asghar, Muhammad S.; Sethi, Sanjeev; Smith, Maxwell L.; Fervenza, Fernando C.; Glassock, Richard J.; Hommos, Musab S.; Rule, Andrew D. Journal of the American Society of Nephrology. 33(10):1927-1941, October 2022.
Broader Screening for Youth-Onset Type 2 Diabetes—We Just Are Not There Yet
Authors: Amy S. Shah, Kristen J. Nadeau, Megan M. Kelsey
Journal: JAMA Network Open (2022)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MA, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Karina W. Davidson, PhD, MASc; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Genetic risk factors have a substantial impact on healthy life years
Authors: Sakari Jukarainen, Tuomo Kiiskinen, Sara Kuitunen, Aki S. Havulinna, Juha Karjalainen, Mattia Cordioli, Joel T. Rämö, Nina Mars, Kaitlin E. Samocha, Hanna M. Ollila, Matti Pirinen, Andrea Ganna
Journal: Nature Medicine (2022)

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.
Rasmussen Aneurysm: A Forgotten Complication
Authors: Stefanie Meiler, Okka W. Hamer, Stefan Blaas, Lukas Luerken
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Rasmussen Aneurysm: A Forgotten Complication." American Journal of Respiratory and Critical Care Medicine, 207(2), pp. 206–207
Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy
Authors: Zinaida Good, Jay Y. Spiegel, Bita Sahaf, Meena B. Malipatlolla, Zach J. Ehlinger, Sreevidya Kurra, Moksha H. Desai, Warren D. Reynolds, Anita Wong Lin, Panayiotis Vandris, Fang Wu, Snehit Prabhu, Mark P. Hamilton, John S. Tamaresis, Paul J. Hanson, Shabnum Patel, Steven A. Feldman, Matthew J. Frank, John H. Baird, Lori Muffly, Gursharan K. Claire, Juliana Craig, Katherine A. Kong, Dhananjay Wagh, John Coller, Sean C. Bendall, Robert J. Tibshirani, Sylvia K. Plevritis, David B. Miklos, Crystal L. Mackall
Journal: Nature Medicine (2022)
Corrigendum to “Albumin binding revitalizes NQO1 bioactivatable drugs as novel therapeutics for pancreatic cancer” [Journal of Controlled Release 349 (2022) 876–889]
Authors: Lei Dou, Huiqin Liu, Kaixin Wang, Jing Liu, Lei Liu, Junxiao Ye, Rui Wang, Haiteng Deng, Feng Qian
Journal: Journal of Controlled Release (2022)
LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization
Authors: Jinyang Hu, Feng Dong, You He, Xianyou Xia, Fangling Cheng, Sui Chen, Xiaoshuang Hou, Po Zhang, Guohao Liu, Ying Li, Qian Gao, Minhai Dong, Ting Li, Wei Li, Qungen Xiao, Xiaopeng Li, Xingjiang Yu, Guifa Xi, Dongsheng Guo, Xudong Wu, Baofeng Wang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Glioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tumor-associated microglia/macrophages (TAMs). Results High level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor prognosis in GBM patients. LRIG2/sLRIGs promotes CD47 expression and facilitates TAM recruitment. Blockade of CD47–SIRPα interactions and inhibition of sLRIG2 secretion synergistically suppress GBM progression in an orthotropic murine GBM model. Conclusions GBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM.
RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAFV600E metastatic colorectal cancer
Authors: Elena Elez, Javier Ros, Jose Fernández, Guillermo Villacampa, Ana Belén Moreno-Cárdenas, Carlota Arenillas, Kinga Bernatowicz, Raquel Comas, Shanshan Li, David Philip Kodack, Roberta Fasani, Ariadna Garcia, Javier Gonzalo-Ruiz, Alejandro Piris-Gimenez, Paolo Nuciforo, Grainne Kerr, Rossana Intini, Aldo Montagna, Marco Maria Germani, Giovanni Randon, Ana Vivancos, Ron Smits, Diana Graus, Raquel Perez-Lopez, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Rodrigo Dienstmann, Josep Tabernero, Rodrigo A. Toledo
Journal: Nature Medicine (2022)

Abstract Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAF V600E colorectal cancer (mCRC BRAF-V600E ). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRC BRAF-V600E treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43 , a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors. Analysis of an independent validation cohort confirmed the relevance of RNF43 mutations to predicting clinical benefit (72.7% versus 30.8%; P = 0.03), as well as longer progression-free survival (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.12–0.75; P = 0.01) and overall survival (HR, 0.26; 95% CI, 0.10–0.71; P = 0.008), in patients with MSS- RNF43 mutated versus MSS- RNF43 wild-type tumors. Microsatellite-instable tumors invariably carried a wild-type-like RNF43 genotype encoding p.G659fs and presented an intermediate response profile. We found no association of RNF43 mutations with patient outcomes in a control cohort of patients with MSS-mCRC BRAF-V600E tumors not exposed to anti-BRAF targeted therapies. Overall, our findings suggest a cross-talk between the MAPK and WNT pathways that may modulate the antitumor activity of anti-BRAF/EGFR therapy and uncover predictive biomarkers to optimize the clinical management of these patients.
A prospective study on myocardial injury after <scp>BNT162b2 mRNA COVID</scp>‐19 fourth dose vaccination in healthy persons
Authors: Nir Levi, Gil Moravsky, Tatyana Weitsman, Itshak Amsalem, Sarit Bar‐Sheshet Itach, Nurit Algur, Ira Lapidus, Ofir Mitz, Michael Glikson, Yonit Wiener‐Well, Tal Hasin
Journal: European Journal of Heart Failure (2022)
In the Wrong Body
Authors: Lori Levy
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Importance of Asking Older Adults Whether They Are Having Difficulty Managing Finances
Authors: Jason Karlawish
Journal: JAMA Network Open (2022)

well-established facts about the problem of cognitive impairment in the US: it is common, and it causes notable harms to the well-being and self-determination of older adults in the US and the friends and families who care for them.The novelty of the study is how the authors examined one of the most serious harms for older adults with cognitive impairment: difficulty managing finances.Not only clinicians but the institutions that hold and manage those adults' financial assets should heed the results by beginning with asking the simple question, "Are you
Label-free metabolic imaging for sensitive and robust monitoring of anti-CD47 immunotherapy response in triple-negative breast cancer
Authors: Minfeng Yang, Arpan Mahanty, Chunjing Jin, Alex Ngai Nick Wong, Jung Sun Yoo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immunotherapy is revolutionizing cancer treatment from conventional radiotherapies and chemotherapies to immune checkpoint inhibitors which use patients' immune system to recognize and attack cancer cells. Despite the huge clinical success and vigorous development of immunotherapies, there is a significant unmet need for a robust tool to identify responders to specific immunotherapy. Early and accurate monitoring of immunotherapy response is indispensable for personalized treatment and effective drug development.We established a label-free metabolic intravital imaging (LMII) technique to detect two-photon excited autofluorescence signals from two coenzymes, NAD(P)H (reduced nicotinamide adenine dinucleotide (phosphate) hydrogen) and FAD (flavin adenine dinucleotide) as robust imaging markers to monitor metabolic responses to immunotherapy. Murine models of triple-negative breast cancer (TNBC) were established and tested with different therapeutic regimens including anti-cluster of differentiation 47 (CD47) immunotherapy to monitor time-course treatment responses using the developed metabolic imaging technique.We first imaged the mechanisms of the CD47-signal regulatory protein alpha pathway in vivo, which unravels macrophage-mediated antibody-dependent cellular phagocytosis and illustrates the metabolism of TNBC cells and macrophages. We further visualized the autofluorescence of NAD(P)H and FAD and found a significant increase during tumor growth. Following anti-CD47 immunotherapy, the imaging signal was dramatically decreased demonstrating the sensitive monitoring capability of NAD(P)H and FAD imaging for therapeutic response. NAD(P)H and FAD intravital imaging also showed a marked decrease after chemotherapy and radiotherapy. A comparative study with conventional whole-body bioluminescence and fluorescent glucose imaging demonstrated superior sensitivity of metabolic imaging. Flow cytometry validated metabolic imaging results. In vivo immunofluorescent staining revealed the targeting ability of NAD(P)H imaging mainly for tumor cells and a small portion of immune-active cells and that of FAD imaging mainly for immunosuppressive cells such as M2-like tumor-associated macrophages.Collectively, this study showcases the potential of the LMII technique as a powerful tool to visualize dynamic changes of heterogeneous cell metabolism of cancer cells and immune infiltrates in response to immunotherapy thus providing sensitive and complete monitoring. Leveraged on ability to differentiate cancer cells and immunosuppressive macrophages, the presented imaging approach provides particularly useful imaging biomarkers for emerged innate immune checkpoint inhibitors such as anti-CD47 therapy.
Risk of Tumor Upstaging With Prostate-Specific Membrane Antigen Positron Emission Tomography in Patients With High-Risk Prostate Cancer
Authors: Aaron Brant, Patrick Lewicki, Michael Xiang, Alec Zhu, Amar U. Kishan, Erqi Liu Pollom, Jonathan E. Shoag
Journal: JAMA Network Open (2022)

This cross-sectional study of data from the National Comprehensive Cancer Network assesses the association of prostate-specific membrane antigen positron emission tomography with tumor upstaging risk in patients with high-risk prostate cancer.
COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis
Authors: Rikke Boedker Holmstroem, Ole Haagen Nielsen, Søren Jacobsen, Lene Buhl Riis, Susann Theile, Jacob Tveiten Bjerrum, Peter Vilmann, Julia Sidenius Johansen, Mogens Karsbøl Boisen, Rikke Helene Løvendahl Eefsen, Inge Marie Svane, Dorte Lisbet Nielsen, Inna Markovna Chen
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis. Patients and methods Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade &gt;1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40. Results Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3–4 treatment-related adverse events, which were manageable and reversible. Conclusions Tocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events. Trial registration number NCT03601611 .